Preparation and use of pyrazole derivatives containing p-fluorophenylthiobipyridine structure

Abstract

The present invention relates to the preparation and use of pyrazole derivatives containing a p-fluorophenylthiobipyridine structure. The pyrazole derivatives are obtained by reacting p-fluorophenylthiobipyridine methyl chloride with pyrazole oxime. The pyrazole derivatives containing a p-fluorophenylthiobipyridine structure show effective control effects on harmful insects, and the compounds are used to prepare insecticides in the fields of agriculture, horticulture, etc.

Description

Technical Field

[0001] The invention relates to the field of chemical pesticides, and in particular to the preparation and use of pyrazole derivatives containing a p-fluorophenylthiobipyridine structure. Background Art

[0002] Pest control and prevention is an important research topic in the pesticide field. In recent years, with the continuous expansion of the use of various pesticides and the increase in the use cycle, some pests have gradually developed resistance to traditional pesticides, and even cross-resistance. At the same time, with the continuous emergence of new pests, it is necessary for pesticide workers to develop new, efficient and low-toxic pesticides.

[0003] Pyrazole compounds, as important nitrogen-containing heterocyclic derivatives, exhibit good insecticidal and acaricidal activities. Among them, the representative compound is fenpyroximate, which is widely used in agricultural production.

[0004]

[0005] At the same time, as an important member of nitrogen-containing heterocyclic rings, substituted pyridine derivatives also have good biological activity and play an important role in the field of plant protection.

[0006] Therefore, in order to further explore and discover compounds with excellent biological activity from pyrazole derivatives, the substituted pyridyl structure is rationally connected to the pyrazole mother nucleus. The present invention discloses a class of pyrazole derivatives containing a p-fluorophenylthiobipyridine structure with agricultural insecticide application value. Summary of the invention

[0007] The purpose of the present invention is to provide a class of pyrazole derivatives containing a p-fluorophenylthiobipyridine structure that have good control effects on a variety of pests and are efficient, safe and environmentally friendly, so as to meet the demand for efficient insecticides in crop protection.

[0008] Another object of the present invention is to provide a method for preparing the above compound.

[0009] Another object of the present invention is to provide the use of the above compound in preparing insecticides.

[0010] In order to solve the above technical problems, the first aspect of the present invention provides a pyrazole derivative containing a p-fluorophenylthiobipyridine structure, which has the following structure:

[0011]

[0012] The second aspect of the present invention provides a method for preparing the above-mentioned pyrazole derivatives containing a p-fluorophenylthiobipyridine structure, which is characterized by comprising the following steps:

[0013]

[0014]

[0015] Among them, the intermediate p-fluorophenylthiobipyridylmethyl chloride can be synthesized by referring to the method in the literature (J.Med.Chem.1998,41,2390-2410); the synthesis of the intermediate pyrazole oxime is synthesized by referring to the conventional method in the literature (Bioorg.Med.Chem.Lett.2016,26,4504-4507).

[0016] The compounds exhibit good control activity against insects, and thus the compounds of the present invention can be used to prepare insecticides to protect agricultural and horticultural plants. The insects include Hemiptera pests such as aphids, brown planthoppers, etc. Of course, the harmful organisms that can be controlled by the compounds of the present invention are not limited to the above examples.

[0017] When the compounds of the present invention are used as pesticides in the fields of agriculture, horticulture, etc., they can be used alone or in the form of pesticide compositions, such as using the compounds as active ingredients and adding pesticide adjuvants commonly used in the art to process them into aqueous emulsions, suspensions, water-dispersible granules, and emulsifiable concentrates.

[0018] Commonly used pesticide adjuvants include: liquid carriers, such as water; organic solvents such as toluene, xylene, cyclohexanol, methanol, butanol, ethylene glycol, acetone, dimethylformamide, acetic acid, dimethyl sulfoxide, animal and vegetable oils and fatty acids; commonly used surfactants such as emulsifiers and dispersants, including anionic surfactants, cationic surfactants, nonionic surfactants and amphoteric surfactants; other adjuvants, such as wetting agents, thickeners, etc.

[0019] When the compound of the present invention is used as an active ingredient in an insecticide, the content in the insecticide is selected within the range of 0.1% to 99.5%, and the appropriate active ingredient content can be determined according to the formulation form and the application method. Usually, the active ingredient is contained in an aqueous emulsion at 5% to 50% (weight percentage, the same below), preferably 10% to 40%; the active ingredient is contained in a suspension at 5% to 50%, preferably 5% to 40%.

[0020] For the use of the insecticide of the present invention, commonly used application methods can be selected, such as foliar spraying, soil treatment and seed treatment, etc. For example, when foliar spraying is adopted, the usable concentration range of the active ingredient compound is 1 to 1000 μg / mL of aqueous emulsion, suspension, water-dispersible granule, emulsifiable concentrate, and the preferred concentration is 1 to 500 μg / mL.

[0021] The pyrazole derivatives containing a p-fluorophenylthiobipyridine structure disclosed in the present invention have good control effects on harmful insects, and thus can be used to prepare insecticides for use in agriculture, horticulture and other fields. DETAILED DESCRIPTION

[0022] The above scheme is further described below in conjunction with specific examples. These examples are used to illustrate the present invention but are not limited to the scope of the present invention. The implementation conditions used in the examples can be further adjusted according to the conditions of the specific manufacturer, and the unspecified implementation conditions are usually the conditions in conventional experiments.

[0023] Embodiment 1:

[0024]

[0025] 6mmol IIIa, 10mmol potassium carbonate and 55mL N,N-dimethylformamide (DMF) were added to a reaction bottle, and 6mmol IIa was added thereto at room temperature. The reaction solution was then heated to 85°C and reacted for 10 hours. After the reaction was completed, the mixture was dried by spin drying, and the residue was separated by column chromatography to obtain the target compound Ia; 1 H NMR (400MHz, CDCl3): δ8.34 (d, J = 2.20Hz, 1H), 7.75 (s, 1H), 7.56~7.60 (m, 2H), 7.33~7.35 (m, 1H), 7.2 1~7.29(m,2H),7.13(t,J=8.60Hz,2H),6.77~6.85(m,3H),4.89(s,2H),3.59(s,3H),2.32(s,3H).HRMS calcd forC 24 H 21 ClFN4O2S[M+H] + 483.1058, found 483.1062.

[0026] Embodiment 2:

[0027]

[0028] 8 mmol of IIIb, 20 mmol of potassium carbonate and 60 mL of acetone were added to a reaction bottle, and 7 mmol of IIa was added thereto at room temperature. The reaction solution was then heated and refluxed for 11 hours. After the reaction was completed, the mixture was dried by spin drying, and the residue was separated by column chromatography to obtain the target compound Ib; 1H NMR (400MHz, CDCl3): δ8.34(d,J=2.30Hz,1H),7.73(s,1H),7.57(d,J=2.90Hz,2H),7.56(d,J=2.40Hz,2H),7.34(d,J=8.20 HRMS calcd for C 24 H 21 FIN4O2S[M+H] + 575.0414, found 575.0417.

[0029] Embodiment 3:

[0030]

[0031] 7 mmol IIIc, 21 mmol triethylamine and 50 mL DMSO were added to a reaction bottle, and 9 mmol IIa was added thereto at room temperature. The reaction solution was then heated to 85°C and reacted for 16 hours. After the reaction was completed, the mixture was dried by spin drying, and the residue was separated by column chromatography to obtain the target compound Ic; 1 H NMR (400MHz, CDCl3): δ8.34 (d, J = 2.30Hz, 1H), 7.74 (s, 1H), 7.51~7.61 (m, 2H), 7.35~7.38 (m, 1H) ,7.05~7.13(m,4H),6.73~6.80(m,3H),4.90(s,2H),3.57(s,3H),2.32(s,3H),2.28(s,3H).HRMS calcd for C 25 H 24 FN4O2S[M+H] + 463.1604, found 463.1606.

[0032] Embodiment 4:

[0033]

[0034] 11mmol IIId, 20mmol potassium carbonate and 30mL N,N-dimethylformamide (DMF) were added to a reaction bottle, and 10mmol IIa was added thereto at room temperature. The reaction solution was then heated to 55°C and reacted for 5 hours. After the reaction was completed, the mixture was dried by spin drying, and the residue was separated by column chromatography to obtain the target compound Id; 1H NMR (400MHz, CDCl3): δ8.30(d,J=2.30Hz,1H),7.72(s,1H),7.53~7.56(m,2H),7.33~7.36(m,1H),7.09(t,J=8.60 HRMS calcd for C 24 H 20 F3N4O2S[M+H] + 485.1259, found 485.1262.

[0035] Embodiment 5:

[0036] Screening of insecticidal activity of compounds against aphids and brown planthoppers

[0037] The spray method proposed by the International Resistance Action Committee (IRAC) was used: the test subjects were aphids and brown planthoppers. The broad bean leaves infected with aphids and the rice seedlings infected with brown planthoppers were sprayed under the Potter spray tower. After treatment, the aphids and brown planthoppers were placed in a 25℃ observation room for cultivation. The results were investigated after 48 hours. The insects were touched with a brush, and no reaction was considered dead. The test concentration was 500μg / mL (other concentrations of the solution can be obtained by diluting the 500μg / mL solution)

[0038] Table 1. Preliminary insecticidal activity data of Ia-Id

[0039]

[0040] “-”: indicates undetermined

[0041] The insecticidal activity test data of compounds Ⅰa~Ⅰd are shown in Table 1. The results show that the target products Ⅰa~Ⅰd all show excellent insecticidal activity. When the test concentration is 500μg / mL, the insecticidal effects of compounds Ⅰa~Ⅰd on aphids are 100%, 100%, 100% and 100%, respectively. When the test concentration is 100μg / mL, the insecticidal rates of compounds Ⅰa~Ⅰd on aphids are 100%, 100%, 100% and 60%, respectively. When the test concentration is 20μg / mL, the control effects of compounds Ⅰa~Ⅰc on aphids are 50%, 60% and 70%, respectively. When the test concentration is 500μg / mL, the insecticidal rates of compounds Ⅰa~Ⅰd on brown planthoppers are 100%, 100%, 100% and 80%, respectively.

[0042] The above experimental data show that by rationally connecting the substituted pyridyl structure to the pyrazole skeleton, the new pyrazole derivatives obtained exhibit good insecticidal activity.

[0043] The above shows and describes the basic principles, main features and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above examples. The above examples and descriptions are only for explaining the principles of the present invention. The present invention may be subject to various changes and improvements without departing from the spirit and scope of the present invention. These changes and improvements fall within the scope of the present invention. The scope of protection of the present invention is defined by the attached claims and their equivalents.

Claims

1. A pyrazole derivative I containing a p-fluorophenylthiobipyridine structure, characterized in that The structure is:

2. The method for preparing the pyrazole derivative I containing a p-fluorophenylthiobipyridine structure according to claim 1, characterized in that Here’s how:

3. Use of the pyrazole derivative I containing a p-fluorophenylthiobipyridine structure as claimed in claim 1 in preparing drugs for killing aphids and brown planthoppers, characterized in that: The derivative I is used alone, or the derivative I is used as an active ingredient and is added with pesticide adjuvants commonly used in the art to be processed into an aqueous emulsion, a suspension, a water-dispersible granule, or an emulsifiable concentrate.

4. Use of the pyrazole derivative I containing a p-fluorophenylthiobipyridine structure as claimed in claim 3 in preparing drugs for killing aphids and brown planthoppers, characterized in that: When the derivative I in claim 1 is used as an active ingredient of aphid and brown planthopper killing drugs, the content of the derivative I in the aphid and brown planthopper killing drugs is selected within the range of 0.1% to 99.5%.

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